Leg ulcers in sickle cell disease.

Sickle cell disease is a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. The manifestations of this disease are protean.Among them, leg ulcers represent a particularly disabling and chronic complication, often associated with a more severe clinical course.Despite the fact that this complication has been recognized since the early times of SCD, there has been little improvement in the efficacy of its management and clinical outcome over the past 100 years. Recently, vasculopathic abnormalities involving abnormal vascular tone and activated, adhesive endothelium have been recognized as another pathway to end organ damage in sickle cell disease. Vasculopathy of sickle cell disease has been implicated in the development of pulmonary hypertension, stroke, leg ulceration and priapism, particularly associated with hemolytic severity, and reported in other severe hemolytic disorders. The authors present the proceedings from the Educational Session on Chronic leg ulcers in Sickle cell disease, held during the 4th Annual Sickle Cell Disease Research and Educational Symposium, on February 17, 2010 in Fort Lauderdale, Fla

Local Causal States and Discrete Coherent Structures

Coherent structures form spontaneously in nonlinear spatiotemporal systems and are found at all spatial scales in natural phenomena from laboratory hydrodynamic flows and chemical reactions to ocean, atmosphere, and planetary climate dynamics. Phenomenologically, they appear as key components that organize the macroscopic behaviors in such systems. Despite a century of effort, they have eluded rigorous analysis and empirical prediction, with progress being made only recently. As a step in this, we present a formal theory of coherent structures in fully-discrete dynamical field theories. It builds on the notion of structure introduced by computational mechanics, generalizing it to a local spatiotemporal setting. The analysis' main tool employs the \localstates, which are used to uncover a system's hidden spatiotemporal symmetries and which identify coherent structures as spatially-localized deviations from those symmetries. The approach is behavior-driven in the sense that it does not rely on directly analyzing spatiotemporal equations of motion, rather it considers only the spatiotemporal fields a system generates. As such, it offers an unsupervised approach to discover and describe coherent structures. We illustrate the approach by analyzing coherent structures generated by elementary cellular automata, comparing the results with an earlier, dynamic-invariant-set approach that decomposes fields into domains, particles, and particle interactions.Comment: 27 pages, 10 figures; http://csc.ucdavis.edu/~cmg/compmech/pubs/dcs.ht

Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140217/1/sur.2013.9999.pd

Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry

Introduction The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers. Methods We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm View™; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI. Results Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had ≥1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145–354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89). Conclusions Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of ≈80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each center’s first cases

Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer

© 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette–Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. Patients and methods: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2: 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.Peer reviewe

Search for Nucleon Decays induced by GUT Magnetic Monopoles with the MACRO Experiment

The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of $\sim 3\cdot 10^{-16} cm^{-2} s^{-1} sr^{-1}$ for $1.1\cdot 10^{-4} \le |\beta| \le 5\cdot 10^{-3}$, based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.Comment: 12 pages, Latex, 10 figures and 2 Table